The urinary bladder is capable of modulating its surface area in response to increased pressure to accommodate a wide range of urine volumes, and the mechanisms that enable these remarkable cells to sense mechanical stimulation and transduce this signal into cellular events are unclear. Umbrella cells, which comprise the most superficial layer of the bladder uroepithelium, may modulate their surface area by the dynamic insertion and removal of discoidal vesicles. We propose to investigate the role of Uroplakin IlIa (UPllla), an important constituent of discoidal vesicles, in umbrella cell discoidal vesicle trafficking. We will explore the requirement for this protein in the bladder response to stretch using UPllla knockout mice. The role of UPllla in the assembly of the bladder asymmetrical unit membrane (AUM) will be studied using a primary cell culture model, and the interactions of this protein with other components of the uroepithelium will be studied to explore the functions of this protein. This is an important area of research because it will further our understanding of cellular responses to mechanical stimuli, while providing insights into the functions of uroplakin proteins and the normal physiology of bladder accommodation of urine.